Translatioanl studies of a bionic pancreas for out-patient diabetes management

描述（由申请人提供）：第一个体外闭环BG （BG）控制系统或仿生内分泌胰腺的最终实施方案可能是一个便携式设备，由三个基本组件组成：连续血糖监测仪（CGM），连续皮下（SC）药物输注装置（例如胰岛素泵）和控制算法。控制算法通过接收来自CGM的葡萄糖数据流，根据该数据流做出治疗决策，并向药物输注装置发出控制剂量，将其他两个组件连接起来。我们在波士顿大学（BU）的糖尿病猪临床前研究和马萨诸塞州总医院（MGH）临床研究中心（CRC）的儿科和成人1型糖尿病患者的临床可行性研究中设计并广泛测试了我们的闭环BG控制系统。在我们的临床前和临床研究中，我们已经测试了我们系统的单胰岛素和双激素（胰岛素和胰高血糖素）配置。虽然我们目前的平台，在笔记本电脑上运行我们的控制算法，是可移动的，但它只允许我们的受试者有限的移动，因为他们在任何时候都被绑在离静脉注射杆两英尺的范围内。为了克服这一限制，我们建立了第一个真正的移动平台，用于在门诊环境中进行过渡性研究，测试仿生内分泌胰腺。该系统围绕iPhone 4S构建，iPhone 4S运行我们的控制算法，并协调CGM、控制算法和胰岛素泵之间的所有通信。我们新的移动设备平台将允许我们从基于crc的可行性研究过渡到门诊过渡研究。此外，我们的新平台高度灵活，允许我们在各种研究队列中测试我们的系统（例如，新诊断，c肽阳性受试者，青春期前受试者等），并使用新的传感器和输液技术，当它们可用时。因此，我们的新平台为我们提供了一个持久的研究工具，使我们能够测试几代新技术，研究新的群体，并为我们的仿生胰腺在形式和功能上进行逐步改进。我们的目标是利用我们新的移动设备平台在门诊环境中进行过渡性研究，并将最终设备规范（包括算法架构、参数设置和用户界面设计）集成到最终的商业产品中，然后在未来的关键研究中进行测试。我们建议使用新的移动设备平台实现这一目标，具体目标如下：(1)在马萨诸塞州巴顿中心的两家糖尿病营进行一项门诊过渡研究，在32名患有1型糖尿病的儿科受试者（7-21岁）中测试我们的设备；(2)在12名患有1型糖尿病的成年受试者（21岁或以上）中进行一项门诊过渡研究，测试我们的设备，这些受试者是从MGH的工作人员中选择的，他们在MGH的日常工作周设置。(3)进行一项门诊过渡性研究，在18名被诊断为1型糖尿病且c肽阳性的受试者（7岁或以上）中测试我们的设备。

DESCRIPTION (provided by applicant): The ultimate embodiment of the first extracorporeal closed-loop BG (BG) control system, or bionic endocrine pancreas, will likely be a portable device consisting of three essential components: a continuous glucose monitor (CGM), a continuous subcutaneous (SC) drug infusion device (e.g. an insulin pump), and a control algorithm. The control algorithm links the other two components by receiving the glucose data stream from the CGM, making a therapeutic decision based on that data stream, and issuing control doses to the drug infusion device. We have designed and extensively tested our closed-loop BG control system in preclinical studies in diabetic swine at Boston University (BU) and in clinical feasibility studies in pediatric and adult subjects with type 1 diabetes in the Clinical Research Center (CRC) at the Massachusetts General Hospital (MGH). In our preclinical and clinical studies, we have tested both insulin-only and bihormonal (insulin and glucagon) configurations of our system. Although our current platform, which runs our control algorithm on a laptop computer, is mobile, it allows our subjects only limited mobility as they are physically tethered to within two feet of an IV pole at all times. To overcome this limitation, we have built the first truly mobile platform for testing a bionic endocrine pancreas in transitional studies in he out-patient setting. The system is built around an iPhone 4S, which runs our control algorithm and coordinates all communication between the CGM, control algorithm, and insulin pump(s). Our new mobile-device platform will allow us to transition from CRC-based feasibility studies to out-patient transitional studies. Furthermore, our new platform is highly flexible and will allow u to test our system in a variety of study cohorts (e.g. new diagnoses, C-peptide positive subjects, pre-adolescent subjects, etc), and with new sensor and infusion technologies, as they become available. As such, our new platform provides us with an enduring research tool that will allow us to test generations of new technologies, study new cohorts, and add progressive improvements in form and function to our bionic pancreas. Our objective is to use our new mobile-device platform to conduct transitional studies in the out-patient setting and to converge upon final device specifications (including algorithm architecture, parametric settings, and user-interface design) for integration into what will become the final embodiment of a commercial product that can be built and then tested in a future pivotal study. We propose to achieve this objective using our new mobile-device platform with the following three specific aims: (1) to conduct an out-patient transitional study testing our device in 32 pediatric subjects (7-21 years old) with type 1 diabetes at the Barton Center's two diabetes camp facilities in Massachusetts, (2) to conduct an out-patient transitional study testing our device in 12 adult subjects (21 years or older) chosen from among the staff at MGH with type 1 diabetes in the setting of their routine work week at MGH, and (3) to conduct an out-patient transitional study testing our device in 18 subjects (7 years or older) who are within three months of diagnosis with type 1 diabetes and who have a positive stimulated C-peptide.